Interactions between malaria and mosquitoes: the role of apoptosis in parasite establishment and vector response to infection.

Malaria parasites of the genus Plasmodium are transmitted from host to host by mosquitoes. Sexual reproduction occurs in the blood meal and the resultant motile zygote, the ookinete, migrates through the midgut epithelium and transforms to an oocyst under the basal lamina. After sporogony, sporozoites are released into the mosquito haemocoel and invade the salivary gland before injection when next the mosquito feeds on a host. Interactions between parasite and vector occur at all stages of the establishment and development of the parasite and some of these result in the death of parasite and host cells by apoptosis. Infection-induced programmed cell death occurs in patches of follicular epithelial cells in the ovary, resulting in follicle resorption and thus a reduction in egg production. We argue that fecundity reduction will result in a change in resource partitioning that may benefit the parasite. Apoptosis also occurs in cells of the midgut epithelium that have been invaded by the parasite and are subsequently expelled into the midgut. In addition, the parasite itself dies by a process of programmed cell death (PCD) in the lumen of the midgut before invasion has occurred. Caspase-like activity has been detected in the cytoplasm of the ookinetes, despite the absence of genes homologous to caspases in the genome of this, or any, unicellular eukaryote. The putative involvement of other cysteine proteases in ancient apoptotic pathways is discussed. Potential signal pathways for induction of apoptosis in the host and parasite are reviewed and we consider the evidence that nitric oxide may play a role in this induction. Finally, we consider the hypothesis that death of some parasites in the midgut will limit infection and thus prevent vector death before the parasites have developed into mature sporozoites.